Mechanisms of muscle steatosis in dysferlinopathy: relationship to interaction of dysferlin and PTRF
We have been engaged for last several years in exploring and understanding how loss of protein(s) leads to loss of adipose tissue, both in animal models and in humans and have developed tools to explore the biology of fat in tissues like the liver and muscle. From this perspective, we have designed experiments to determine why a few muscles, like psoas, in dysferlin-deficient mice, accumulate lipids and to measure the deleterious effect of lipid accumulation in muscle function. We will also study how additional protein(s) interact with dysferlin protein and cause muscle dysfunction in mice and humans with dysferlin-deficiency. Such studies will define two important aspects: a) molecular mechanism(s) for muscle lipid accumulation and b) protein partners of dysferlin, aiding in further designing the therapeutic approaches for the treatment of patients with dysferlinopathy.